Human papillomavirus (HPV) infection is a primary risk factor for cervical cancer. However, infection alone does not lead to cancer in all cases. Data suggest that immune factors play a central role in controlling cervical disease progression. Studies have shown that an impaired T-cell proliferative response to specific HPV16 peptides is associated with a failure to resolve HPV infection and persistent cervical disease. The relation between immune function and cervical disease is particularly relevant given the following set of observations: 1) Receipt of an abnormal Pap test result is a stressful event that can lead to increased distress and disruptions in major life areas; and 2) Psychological responses to stress are associated with immunologic changes. Over the past few years, we have been conducting preliminary studies of psychosocial and behavioral correlates of T-cell response to specific HPV16 peptides among women with cervical dysplasia. Our findings suggest that higher levels of stress are associated with an impaired T-cell response to HPV, even after controlling for key behavioral risk factors. However, any causal effects of psychosocial factors on HPV-specific immune response still remain to be demonstrated. Therefore, in a randomized trial, we plan to evaluate the biobehavioral effects of a well-established, standardized Mindfulness-Based Stress Reduction (MBSR) program in women with cervical dysplasia. MBSR is highly accessible across diverse socioeconomic and cultural groups and has demonstrated beneficial effects on psychosocial and emotional well-being in a variety of patient and healthy populations. In the proposed study, 300 women with cervical dysplasia will be randomly assigned to the MBSR program or an attention control condition. The primary aims of the study are to examine the effects of MBSR on psychosocial well-being (e.g., perceived stress, quality of life) and HPV-specific immune functioning (e.g., T-cell response to HPV16 E6, E7, and L1 peptides, intracellular cytokine expression in HPV-stimulated T cells) compared to the control condition at post-intervention and follow-up time points. It is hypothesized that MBSR participants will report lower levels of perceived stress, higher quality of life, and enhanced HPV-specific immune response (i.e. greater proliferative response to HPV16 and greater expression of Th1 cytokines) compared to control participants at post-intervention and subsequent follow-up time points. A secondary aim is to examine the extent to which changes in psychosocial well-being may mediate any effects of the intervention on HPV- specific immune response. RELEVANCE: The proposed project will be one of the first to examine whether psychosocial factors can directly influence the biological processes that are responsible for controlling cervical disease. Such findings would have clinical implications for the management of women at risk for cervical cancer.